Survival analysis in heart transplantation: results from an analysis of 1290 cases in a single center

Background: The clinical profiles of recipients and donors eligible for the procedure as well as the procedure itself have changed over time. We determined the impact of changes in baseline risk profiles at different transplant periods on outcome, and the time-specific distribution of causes of death. Patients and methods: Adult heart transplantations were performed consecutively on 1290 patients. Three transplant periods were defined: 1989–1993, 1994–1998, and 1999–2004. Results: Recipient age and body mass index, previous cardiac surgery, high urgency status, need of ventricular assist device, waiting time (to transplantation and on ventricular assist device), donor age and body mass index, donor–recipient body mass index mismatch, and ischemic and cardiopulmonary bypass time were significantly different over the three transplant periods. There was, however, no significant difference in mortality risk. The major causes of deaths were: acute rejection, multiorgan failure, and right heart failure (≤30 days); infection and acute rejection (31 days to 1 year); malignancy, acute rejection, and cardiac allograft vasculopathy (>1–5 years); cardiac allograft vasculopathy and malignancy (>5–10 years); and malignancy and infection (>10 years). The overall 1-, 5-, 10- and 15-year survival was respectively 77%, 67%, 53% and 42%. There was no difference in survival by different transplant periods (p = 0.68). Conclusion: Despite clearly increased baseline risk profiles over time, the outcome of adult heart transplantation remains stable and encouraging. Cardiac allograft vasculopathy, malignancy, and infection threaten the long-term survival.     

Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study.

BACKGROUND: Cardiac retransplantation is a controversial procedure due to the disparity between donor heart demand and supply. METHODS: Of 7,290 patients undergoing primary cardiac transplantation between January 1990 and December 1999 at 42 institutions contributing to the Cardiac Transplant Research Database (CTRD), 106 patients later underwent a second and 1 patient a third cardiac transplant procedure. RESULTS: The actuarial freedom from retransplantation was 99.2% and 96.8% at 1 and 10 years, respectively. Reasons for retransplantation included early graft failure (n = 34), acute cardiac rejection (n = 15), coronary allograft vasculopathy (CAV, n = 39), non-specific graft failure (n = 7), and miscellaneous (n = 10). The only risk factor associated with retransplantation was younger age, reflecting the policy of preferential retransplantation of younger patients. Survival after retransplantation was inferior to that after primary transplantation (56% and 38% at 1 and 5 years, respectively). Risk factors associated with death after retransplantation included retransplantation for acute rejection (p = 0.0005), retransplantation for early graft failure (p = 0.03), and use of a female donor (p = 0.005). Survival after retransplantation for acute rejection was poorest (32% and 8% at 1 and 5 years, respectively) followed by retransplantation for early graft failure (50% and 39% at 1 and 5 years, respectively). Survival after retransplantation for CAV has steadily improved with successive eras. CONCLUSIONS: The results of retransplantation for acute rejection and early graft failure are poor enough to suggest that this option is not advisable. However, retransplantation for CAV is currently associated with satisfactory survival and should continue to be offered to selected patients.     

Pediatric cardiac retransplantation: intermediate-term results

BACKGROUND: Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy. METHODS: Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years). RESULTS: Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70). CONCLUSIONS: Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation.     

Should we perform heart retransplantation in early graft failure?

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure ( n  = 11) or late graft failure (acute rejection: n  = 2, transplant-related coronary artery disease: n  = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than ( n  = 11, all in early graft failure) or more than ( n  = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively ( P  = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria.     

Cardiac retransplantation: is it justified in times of critical donor organ shortage? Long-term single-center experience

Objective: Survival after heart transplantation has improved significantly over the last decades. There are a growing number of patients that require cardiac retransplantation because of chronic allograft dysfunction. With regard to the critical shortage of cardiac allograft donors the decision to offer repeat heart transplantation must be carefully considered. Methods: Since 1983 a total of 807 heart transplantations have been performed at our institution. Among them 41 patients received cardiac retransplantation, 18 patients because of acute graft failure and 23 because of chronic graft failure. Data were analyzed for demographics, morbidity and risk factors for mortality. The acute and chronic retransplant group was compared to those patients undergoing primary transplantation. Results: The mean interval between primary transplantation and retransplantation was 1.9 days in the acute and 6.7 years in the chronic retransplant group. Mean follow-up was 6.9 years. Baseline characteristics were similar in the primary and retransplant group. Actuarial survival rates at 1, 3, 5 and 7 years after primary cardiac transplantation compared to retransplantation were 83, 78, 72 and 64% vs 53, 50, 47 and 36%, respectively (p < 0.001). Early mortality after acute retransplantation was significantly higher compared to late retransplantation (10/18, 55.6% vs 4/23, 17.4%, p = 0.011). Major causes of death were acute and chronic rejection, infection and sepsis. Conclusions: Cardiac retransplantation is associated with lower survival rates compared to primary transplantation. However, results after retransplantation in chronic graft failure are significantly better compared to acute graft failure. Therefore, we consider cardiac retransplantation in chronic graft failure a justified therapeutic option. In contrast, patients with acute graft failure seem to be inappropriate candidates for cardiac retransplantation.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Heart retransplantation for heart allograft failure in Chinese heart transplant recipients: NTUH experience

We investigated the short- and long-term results after heart retransplantation in terms of different causes of heart allograft failure. We sought to establish the data of heart retransplantation in Chinese compared with Western counterparts due to differences in heart allograft vasculopathy. From March 1995 to May 2005, eight heart transplantation recipients with allograft failure underwent retransplantation. Heart allograft failure was due to coronary vasculopathy (CAV) in six patients (75%) and acute rejection in two patients (25%). The mean interval to retransplantation was 32 to 84 months (mean 54.3 months). There were five patients who survived after heart retransplantation for CAV and no patient survived after an earlier diagnosis of acute rejection. Heart retransplantation is a feasible method with acceptable long-term survival rate for heart allograft failure. After careful pretransplant evaluation, retransplantation is acceptable. The survival after retransplantation for CAV is notably great than that after acute rejection. Heart retransplantation is the only way for patients who have cardiac allograft failure to achieve long-term survival.     

Jugular venous valved conduit (Contegra) matches allograft performance in infant truncus arteriosus repair

Objective: Limited availability and durability of allograft conduits require that alternatives be considered. We compared bovine jugular venous valved (JVV) and allograft conduit performance in 107 infants who survived truncus arteriosus repair. Methods: Children were prospectively recruited between 2003 and 2007 from 17 institutions. The median z-score for JVV (n = 27, all 12 mm) was +2.1 (range +1.2 to +3.2) and allograft (n = 80, 9–15 mm) was +1.7 (range −0.4 to +3.6). Propensity-adjusted comparison of conduit survival was undertaken using parametric risk-hazard analysis and competing risks techniques. All available echocardiograms (n = 745) were used to model deterioration of conduit function in regression equations adjusted for repeated measures. Results: Overall conduit survival was 64 ± 9% at 3 years. Conduit replacement was for conduit stenosis (n = 16) and/or pulmonary artery stenosis (n = 18) or regurgitation (n = 1). The propensity-adjusted 3-year freedom from replacement for in-conduit stenosis was 96 ± 4% for JVV and 69 ± 8% for allograft (p = 0.05). The risk of intervention or replacement for branch pulmonary artery stenosis was similar for JVV and allograft. Smaller conduit z-score predicted poor conduit performance (p < 0.01) with best outcome between +1 and +3. Although JVV conduits were a uniform diameter, their z-score more consistently matched this ideal. JVV exhibited a non-significant trend towards slower progression of conduit regurgitation and peak right ventricular outflow tract (RVOT) gradient. In addition, catheter intervention was more successful at slowing subsequent gradient progression in children with JVV versus those with allograft (p < 0.01). Conclusions: JVV does match allograft performance and may be advantageous. It is an appropriate first choice for repair of truncus arteriosus, and perhaps other small infants requiring RVOT reconstruction.     

Early and late outcomes after cardiac retransplantation

Background

Cardiac retransplantation remains the most viable option for patients with allograft heart failure; however, careful patient selection is paramount considering limited allograft resources. We analyzed clinical outcomes following retransplantation in an academic, tertiary care institution.

Methods

Between 1981 and 2011, 593 heart transplantations, including 22 retransplantations were performed at our institution. We analyzed the preoperative demographic characteristics, cause of allograft loss, short- and long-term surgical outcomes and cause of death among patients who had cardiac retransplantations.

Results

Twenty-two patients underwent retransplantation: 10 for graft vascular disease, 7 for acute rejection and 5 for primary graft failure. Mean age at retransplantation was 43 (standard deviation [SD] 15) years; 6 patients were women. Thirteen patients were critically ill preoperatively, requiring inotropes and/or mechanical support. The median interval between primary and retransplantation was 2.2 (range 0–16) years. Thirty-day mortality was 31.8%, and conditional (> 30 d) 1-, 5- and 10-year survival after retransplantation were 93%, 79% and 59%, respectively. A diagnosis of allograft vasculopathy (p = 0.008) and an interval between primary and retransplantation greater than 1 year (p = 0.016) had a significantly favourable impact on 30-day mortality. The median and mean survival after retransplantation were 3.3 and 5 (SD 6, range 0–18) years, respectively; graft vascular disease and multiorgan failure were the most common causes of death.

Conclusion

Long-term outcomes for primary and retransplantation are similar if patients survive the 30-day postoperative period. Retransplantation within 1 year of the primary transplantation resulted in a high perioperative mortality and thus may be a contraindication to retransplantation.     

Cardiac retransplantation: a 15-year single-center clinical experience

BACKGROUND: Cardiac retransplantation is a controversial therapy because of the shortage of donor hearts. We retrospectively reviewed the short-term and long-term outcomes after cardiac retransplantation. METHODS AND RESULTS: Twenty-eight cases (18 males, 7 females; mean age, 50.3 +/- 13.5 years) underwent cardiac retransplantation: 25 first retransplantations and 3 second retransplantations. The indications for retransplantation were primary graft failure (PGF) in 11 patients (39.3%), intractable acute cardiac rejection (IACR) in 4 patients (14.3%), and coronary allograft vasculopathy (CAV) in 13 patients (46.4%). The patients had been supported as follows: prolonged cardiopulmonary bypass (CPB; n = 3), intra-aortic balloon pumping (IABP; n = 1), intravenous inotropic support (n = 7), extracorporeal membranoxygenator (ECMO; n = 3), ventricular assist device (VAD; n = 4), and no inotropic support (n = 10). There were 8 deaths within 30 days after retransplantation (28.6%). The overall 1-, 5-, 10-, and 15-year survival rates were 46.4%, 40.6%, 32.5%, and 32.5%, respectively. Acute cardiac rejection was the most common cause of death (43.8%). Thirty-day and 1-year survival rates of IACR, PGF, and CAV were 50.0%/0%, 63.6%/45.5%, and 84.6%/68.4%, respectively. CONCLUSIONS: Long-term survival after retransplantation was acceptable for patients with CAV and PGF; however, we must select patients for retransplantation carefully if the indication is IACR, because of the poor outcome.     

Heart Retransplantation

Retransplants comprise only a small minority (3-4%) of heart transplants, however outcome following retransplantation is compromised. Risk factors for a poor outcome following retransplantation include retransplantation early (<6 months) after primary transplant, retransplantation for acute rejection or early allograft failure, and retransplantation in an earlier era. The incidence of rejection and infection is similar following primary transplant and retransplantation. The compromised outcomes and risk factors for a poor outcome are similar in adult and pediatric heart retransplantation. However, due to the short half-life of the transplanted heart, it is an expectation that patients transplanted in childhood may require retransplantation. Based on the data available and the opinion of the working group, indications for heart retransplantation are (i) chronic severe cardiac allograft vasculopathy with symptoms of ischemia or heart failure (should be considered) or asymptomatic moderate or severe left ventricular dysfunction (may be considered) or (ii) chronic graft dysfunction with symptoms of progressive heart failure in the absence of active rejection. Patients with graft failure due to acute rejection with hemodynamic compromise, especially <6 months post-transplant, are inappropriate candidates for retransplantation. In addition, guidelines established for primary transplant candidacy should be strictly followed.     

Inhaled iloprost to control residual pulmonary hypertension following pulmonary endarterectomy

Objective: Pulmonary endarterectomy (PEA) is the standard therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In the immediate postoperative period, persistent pulmonary hypertension increases the risk of acute respiratory or right heart failure. In pulmonary arterial hypertension, prostanoid inhalation has been found to improve pulmonary hemodynamics, right ventricular function, gas exchange, and clinical outcome. We report the results of a double-blinded randomized trial with the aerosolized prostacyclin analogue iloprost in patients with residual pulmonary hypertension after PEA. Methods: Twenty-two patients (age, 55 ± 13 years; 8 females; propofol- and sufentanil-based anesthesia; pressure-controlled mechanical ventilation) were randomized to receive either a single dose of 25 μg aerosolized iloprost (iloprost group; n = 11) or normal saline (placebo group; n = 11) immediately after postoperative ICU admission. Primary endpoints were changes in gas exchange, pulmonary and systemic hemodynamics, and clinical outcome. Results: Iloprost significantly enhanced cardiac index (CI) and reduced mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance [PVR (dyn s cm⁻⁵)] in contrast to placebo. Placebo: pre-inhalation 413 ± 195 versus post-inhalation 404 ± 196 at 30 min (p = 0.051), 415 ± 189 at 90 min (p = 0.929). Iloprost: pre-inhalation 503 ± 238 versus post-inhalation 328 ± 215 at 30 min (p = 0.001), 353 ± 156 at 90 min (p = 0.003). Blood oxygenation remained unchanged. Conclusion: In addition to the effect of PEA, iloprost reduces residual postoperative pulmonary hypertension, decreases right ventricular afterload and may facilitate the early postoperative management after PEA.     

Long-term survival after cardiac retransplantation: a twenty-year single-center experience

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.     

The results of cardiac retransplantation: an analysis of the Joint International Society for Heart and Lung Transplantation/United Network for Organ Sharing Thoracic Registry

BACKGROUND: It is well established that repeat heart transplantation has a significantly worse outcome when compared with primary (first time) transplantation. Defining the risk factors for mortality within this group has been difficult due to small numbers of patients at individual centers. METHODS: All cardiac retransplants performed in the United States and registered in the Joint International Society for Heart and Lung Transplantation (ISHLT)/United Network for Organ Sharing (UNOS) Thoracic Registry were analyzed for demographics, morbidity posttransplantation, immunosuppression, and risk factors for mortality. RESULTS: The study cohort included 514 patients of which 81% were male with a mean age of 47+/-12 years. Time from primary transplant to retransplantation ranged from 1 day to 15.5 years and more than 50% of the patients underwent retransplantation for chronic rejection. More than 60% of patients were in the intensive care unit at the time of retransplantation and more than 40% of the patients were reported to be on some form of life support (ventricular assist device, ventilator, and/or inotropic therapy). Survival for the entire retransplant cohort was 65, 59, and 55% for 1, 2, and 3 years, respectively, but was substantially lower when the intertransplant interval was short. Conversely, when the interval between primary and retransplantation was more than 2 years, 1 year survival postretransplantation approached that of primary transplantation. Additional independent risk factors for mortality for the retransplant cohort included overall cardiac transplant center volume, the use of a ventricular assist device or ventilator, the patient being in the intensive care unit, and recipient age. The four most common causes of death were infection, primary/nonspecific graft failure, chronic rejection (allograft vasculopathy), and acute rejection. CONCLUSIONS: The data confirm that repeat heart transplantation is a higher risk procedure than primary transplantation, especially early after the primary heart transplant.     

Risk factors for reoperation after relief of congenital subaortic stenosis

Background: Congenital subaortic stenosis entails a lesion spectrum, ranging from an isolated obstructive membrane, to complex tunnel narrowing of the left outflow associated with other cardiac defects. We review our experience with this anomaly, and analyze risk factors leading to restenosis requiring reoperation. Methods: From 1994 to 2006, 58 children (median age 4.3 years, range 7 days–13.7 years) underwent primary relief of subaortic stenosis. Patients were divided into simple lesions (n = 43) or complex stenosis (n = 15) associated with other major cardiac defects. Age, pre- and postoperative gradient over the left outflow, associated aortic or mitral valve insufficiency, chromosomal anomalies, arteria lusoria, and operative technique (membrane resection (22) vs associated myectomy (34) vs Konno (2)) were analyzed as risk factors for reoperation (Kaplan–Meier, Cox regression). Results: There was no operative mortality. Median follow-up spanned 2.7 years (range 0.1–10), with one late death at 4 months. Reoperation was required for recurrent stenosis in 11 patients (19%) at 2.6 years (range 0.3–7.5) after initial surgery. Risk factors for reoperation included complex subaortic stenosis (p = 0.003), younger age (p = 0.012), postoperative residual gradient (p = 0.019), and the presence of an arteria lusoria (p = 0.014). For simple lesions, no variable achieved significance for stenosis recurrence. Conclusions: Surgical relief of congenital subaortic stenosis, even with complex defects, yields excellent results. Reoperation is not infrequent, and should be anticipated with younger age at operation, complex defects, residual postoperative gradient, and an arteria lusoria. Myectomy concomitant to membrane resection, even in simple lesions, does not provide enhanced freedom from reoperation, and should be tailored to anatomic findings.     

Post-transplant diabetes mellitus in lung transplant recipients: incidence and risk factors

Objective: Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. Patients and methods: The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. Results: Mean follow-up for all patients was 25 ± 10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57 ± 15 vs 53 ± 13 years, p = 0.009), had increased BMI (26 ± 5 vs 24 ± 4, p = 0.0001), shorter time from diagnosis to LTX (21 ± 13 vs 28 ± 18 months, p = 0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p = 0.72). Conclusions: Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.     

Cardiac retransplantation in childhood: analysis of data from the United Network for Organ Sharing

OBJECTIVE: For children in whom graft failure develops after cardiac transplantation, retransplantation is often considered. Although some centers have reported equivalent results for retransplantation as for primary transplantation, this strategy remains controversial. We sought to examine outcomes after retransplantation in children and to identify risk factors for mortality. METHODS: United Network for Organ Sharing records of heart transplantation for subjects younger than 18 years from 1987 to 2004 were reviewed. Indications for retransplantation and patient characteristics were evaluated. Analysis was performed with proportional hazards regression, controlling for other potential risk factors. RESULTS: Among the 4227 pediatric heart transplants, there were 219 retransplants. The most common indication for retransplantation was coronary allograft vasculopathy (51%). The mean interval from initial heart transplant to retransplantation was 4.7 +/- 3.8 years. Forty-two retransplants (19%) were performed within 180 days of primary transplantation. Survivals at 1, 5, and 10 years after retransplantation were 79%, 53%, and 44%, respectively. In multivariate analysis, retransplantation was associated with significantly higher mortality than primary transplantation (odds ratio 1.67, 95% confidence interval 1.32-2.12, P < .001). Patients who underwent retransplantation within 180 days of primary transplantation had a significantly lower 1-year survival than did other retransplant recipients (53% vs 86%, respectively, P < .02). Subjects who required mechanical ventilation before retransplantation also had poorer survival (P < .03). CONCLUSION: Survival after cardiac retransplantation in children is inferior to that after primary transplantation. Although results are acceptable, the impact of retransplantation on the availability of donor hearts requires further consideration.     

The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia–reperfusion injury

Objective: Ischemia–reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H₂S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H₂S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.     

Kidney Retransplantation: Removal or Persistence of the Previous Failed Allograft?

A significant percentage of patients with failed renal graft are candidates for retransplantation. The outcomes of retransplantation are poorer than those of primary transplantation and sensitization is documented to be a major reason. The management of a failed allograft that is not immediately symptomatic is still very controversial. The aim of this study was to determine the impact of the failed allograft nephrectomy on a subsequent transplantation and its importance in the sensitization. We performed a retrospective analysis of the local prospective transplantation registry of the outcome of 126 second kidney transplantations among 2438 transplantations performed in our unit between June 1980 and March 2013, comparing those who underwent allograft nephrectomy prior to retransplantation with those who retained the failed graft. Primary endpoints were graft and patient survival. The levels of panel-reactive antibodies (PRA) and rate of acute rejections on retransplantation outcomes were also studied. Among the 126 patients who underwent a second renal transplantation, 76 (60.3%) had a prior graft nephrectomy (Group A), whereas 50 (39.7%) kept their failed graft (Group B). Group A showed significantly more positive PRA levels when compared with the other group (38% vs 10%; P < .001), as measured before the most recent transplantation, and a higher rate of acute rejection (19% vs 5.6%; P = .016). There were 28 (36%) renal allograft losses for Group A and 18 (36%) for those who had not had transplantectomy (P = not significant [NS]). One-, 3-, and 5-year graft survival rates were 96.6%, 90.7%, and 83.4%, respectively, in Group A and 95%, 82%, and 68.4%, respectively, in Group B, with no statistical differences (P = .19). Five-year actuarial patient survival rates in the 2 groups was 89.3% and 82.8%, respectively (P = .55). Multivariate analysis showed that PRA level and delayed graft function (DGF) had a statistically significant influence on graft survival (P = .028; odds ratio [OR] = 1.029; and P = .024; OR = 8.6), irrespective of whether the patient had graft nephrectomy or not. The allosensitization indicated by PRA increases after transplantectomy and leads to a higher incidence of acute rejection after retransplantation. Nephrectomy of failed allograft does not seem to significantly influence the survival of a subsequent graft. The decision to remove or retain a failed graft in the context of retransplantation should thus be based on known clinical indications for the procedure.     

Prognostic value of FDG uptake in early stage non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) has a poor prognosis even for early stages of the disease (stage I and II). We studied the prognostic value of PET FDG in patients with completely resected stage I and II NSCLC. Methods: Retrospective study of 96 patients with NSCLC whose staging included ¹⁸F-FDG PET (fluoro deoxy glucose positron emission tomography). Histopathological stage was either stage I (75) or stage II (n = 21). FDG uptake was measured as maximal standardized uptake value for body weight (SUVmax). Mean follow-up was 45 ± 30 months (1–142 months). Overall and cancer-free survival rates were recorded. Results: SUVmax were higher for stage II than for stage I (10.5 ± 4.5 vs 8.5 ± 5, p = 0.04). Mean tumor volumes were equivalent for both stages (33 cm³, p = 0.18), excluding a partial volume effect. The median SUVmax in the whole study population was 7.8. The median survival was significantly longer in patients with a lower (SUVmax ≤ 7.8) FDG uptake (127 months vs 69 months, p = 0.001). For stage I tumors (n = 75), high FDG uptake was significantly associated with reduced median survival: 127 months if SUVmax ≤ 7.8 and 69 months if SUVmax > 7.8 (p = 0.001). For stage II tumors (n = 21), no statistical difference was observed: 72 months vs 40 months for SUVmax ≤ 7.8 and for SUVmax > 7.8, respectively (p = 0.11), although there was a clear trend towards reduced survival for highly metabolic tumors. Disease-free survival was also significantly better for lower metabolic tumors: 96.1 months vs 87.7 months (p = 0.01). Conclusion: High FDG uptake is associated with reduced overall survival and disease-free survival of patients with completely resected stage I–II NSCLC. Whether patients with highly metabolic tumors should undergo a closer postoperative surveillance or adjuvant chemotherapy has to be addressed in a properly designed prospective trial.